First-in-human study of lomvastomig, a PD-1-TIM-3 bispecific antibody, in patients with advanced and/or metastatic solid tumors
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: BACKGROUND: This first-in-human clinical study explored lomvastomig, an immunoglobulin G1-based Fc-silenced bispecific antibody that simultaneously blocks the immune checkpoint receptors programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin domain-3. METHODS: Lomvastomig was characterized in cell cultures and preclinically in cancer mouse models. The phase 1, open-label, multicenter clinical study of lomvastomig included a dose-escalation part in patients with advanced and/or metastatic solid tumors and an expansion part with four tumor-specific cohorts, which enrolled checkpoint inhibitor (CPI)-experienced patients with melanoma and non-small-cell lung cancer (NSCLC) and CPI-naïve patients with SCLC and esophageal squamous cell carcinoma (ESCC). Primary and secondary objectives included safety/tolerability, maximum tolerated dose (MTD)/recommended dose for expansion (RDE), pharmacokinetics, drug receptor occupancy, and antitumor activity. RESULTS: 39 and 95 patients were enrolled in the dose-escalation and expansion parts, respectively. Lomvastomig was well tolerated up to the highest tested dose of 2,100 mg every 2 weeks (Q2W). One dose-limiting toxicity was reported at 1,200 mg (grade 3 troponin T increase). No MTD was reached, and 2,100 mg Q2W was established as the RDE. Linear pharmacokinetics across the studied dose range suggested target saturation. Peripheral blood drug receptor occupancy on CD3+ and CD8+ was saturated at >90% throughout treatment for doses ≥70 mg. Objective responses were observed at 2,100 mg lomvastomig during dose-escalation (21%; n=19), and in the CPI-experienced melanoma (8%, n=38) and CPI-naïve ESCC (20%, n=15) expansion cohorts. CONCLUSIONS: Lomvastomig had a tolerable and manageable safety profile at 2,100 mg Q2W. Clinical activity was limited in CPI-experienced patients with melanoma and NSCLC, while an encouraging signal was observed in CPI-naïve patients with ESCC. TRIAL REGISTRATION NUMBER: NCT03708328 (registration date: 2018-10-09).
Authors: Kristoffer Staal Rohrberg, Ignacio Melero, Miguel F Sanmamed, Eva Muñoz-Couselo, Andrés Cervantes, Valentina Gambardella, Laurent Greillier, Pilar Garrido, Hye Ryun Kim, Dae Ho Lee, Antoine Italiano, Philippe Alexandre Cassier, Sandrine Hiret, Sanjeev Deva, Tae Min Kim, George R Blumenschein, Rikke Løvendahl Eefsen, Brian S Henick, Mario Perro, Pablo Umaña, Antonio Peixoto, Laura Lauener, Patrick Weber, Stefan Seeber, Christian Klein, Brian Higgins, Micol Guidi, Dominik Kraus, Merlind Mücke, Christian Heichinger, Vu-Long Tran, Daniela Schmid, Francesca Michielin, Ting Liu, Christine McIntyre, Henry Kao, Laura Codarri Deak, Christoph Markert, Victor Moreno
Institutions: Rigshospitalet, University of Oxford, Clinica Universidad de Navarra, Centro de Investigación Médica Aplicada, Vall d'Hebron Hospital Universitari, INCLIVA Health Research Institute, Centro de Investigación Biomédica en Red de Cáncer, Aix-Marseille Université, Hospital Universitario Ramón y Cajal, Yonsei University, Yonsei University Health System, University of Ulsan, Université de Bordeaux, Institut Bergonié, Centre Léon Bérard, Institut de Cancérologie de l'Ouest, Auckland City Hospital, Seoul National University Hospital, The University of Texas MD Anderson Cancer Center, Herlev Hospital, Columbia University Irving Medical Center, Roche (Switzerland), Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, Roche Pharma AG (Germany), Ludwig-Maximilians-Universität München, Genentech, Roche (United Kingdom), Hospital Universitario Fundación Jiménez Díaz
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
Funder: F. Hoffmann-La Roche
OpenAlex ID: W7165180277